Journal of Blood Medicine最新文献

Relapsed/refractory multiple myeloma (RRMM) and extramedullary multiple myeloma (EMM) present significant challenges for patients with multiple myeloma (MM) after their disease progresses.Despite notable advancements in treatments like autologous hematopoietic stem cell transplantation (ASCT) and chimeric antigen receptor (CAR)-T-cell therapy, most patients with RRMM and EMM face a short survival period. Currently, there are no effective treatments available. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the treatment options for MM. Reduced-intensity conditioning (RIC) regimens have largely replaced myeloablative conditioning (MAC) regimens. RIC is now preferred because it significantly lowers transplant-related mortality, which has dropped to 10-20%. However, RIC regimens are linked to higher relapse rates compared to MAC. To enhance the efficacy of allo-HSCT, it is essential to identify a safer and more effective conditioning regimen. We report a case of EMM involving the breast, supraclavicular region, mediastinum, and pleural effusion, among other sites. The patient did not respond to several treatments, including a proteasome inhibitor (PI) like bortezomib, immunomodulatory drugs (IMiDs) such as lenalidomide, and a monoclonal antibody targeting CD38, like daratumumab. Consequently, we recommended haploidentical hematopoietic stem cell transplantation as a salvage treatment. After undergoing allo-HSCT with a conditioning regimen that mainly included selinexor and helical tomotherapy, the patient achieved a complete remission(CR) and enjoyed long-term disease-free survival for 11 months. Along with existing literature, this case provides encouraging insights for future research on RRMM and EMM, and we anticipate more reports on allo-HSCT cases in the future.

Purpose: Vietnam is estimated to have approximately 30,000 hemophilia B (HB) carriers, with hundreds of new cases registered annually. However, comprehensive molecular studies on HB remain limited. Therefore, this study aimed to characterize genetic variants and assess their clinical significance in unrelated Vietnamese patients with HB.

Patients and methods: This study included a cohort of 143 unrelated HB patients with diagnosed FIX levels. Genetic analysis of the F9 gene was performed using DNA sequencing and other molecular techniques. Variant pathogenicity was classified following ACMG/AMP guidelines, supplemented by computational predictions and clinical data.

Results: A 100% variant detection rate was achieved, identifying 83 unique variants from 143 patients. Single nucleotide variants were predominant, with missense variants accounting for 71.08%. Of the 83 unique variants, 20 novel variants were identified, including six missenses, four nonsenses, four frameshifts, two large deletions, two in-frame deletions, and two splice-site variants. The serine protease domain contained the highest proportion of variants (49.4%). Pathogenicity analysis revealed a predominance of severe phenotypes (72.03%). Among the novel variants, twelve were classified as pathogenic, one as likely pathogenic, and seven as variants of uncertain significance. A noteworthy case was the NM_000133.4:c.-21C>T promoter variant associated with HB Leyden, which demonstrated age-dependent improvements in factor IX levels.

Conclusion: This study expands the mutational spectrum of HB in the Vietnamese population and provide critical insights into genotype-phenotype correlations. The identification of novel variants enhances diagnostic precision and underscores the importance of comprehensive genomic analyses in understanding disease mechanisms.

Objective: Haploidentical (haplo-) hematopoietic stem cell transplantation (HSCT) has been a standard treatment for hematological malignancies for decades. However, it remains unreimbursable in Thailand due to resource constraints. Only one-fifth of the patients suitable for HSCT in our center had matched donors. Since October 2020, haplo-HSCT has been initiated for patients without matched donors using hospital funding, as it is not reimbursed by the national health policy. This cohort study aimed to demonstrate the clinical outcomes, identify problems, manage complications, adjust the protocol of haplo-HSCT in Thailand, and advocate for making haplo-HSCT accessible for treatment in developing countries.

Methods: Due to financial constraints, only eight patients with 6 acute myeloid leukemia, 1 acute lymphoblastic leukemia, and 1 lymphoma received haplo-HSCT in the first year. Unmanipulated peripheral blood stem cell haplo-HSCT was performed with post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GvHD) prophylaxis.

Results: All patients experienced cytokine release syndrome (CRS) grade 1-2 which improved after PTCy administration. One patient with active disease and HLA-DRB1 mismatch had worsening CRS after PTCy and required tocilizumab treatment. Two patients had grade 3 acute GvHD while a patient developed moderate chronic GvHD. Half of the patients had CMV viremia which was controlled with ganciclovir. At a median follow-up of 7.7 months, 7 patients were alive in remission.

Conclusion: Haplo-HSCT is a feasible treatment option for hematological malignancies, yielding satisfactory outcomes with controllable side effects. Enhanced monitoring and early intervention strategies can further improve patient outcomes. Advocating for haplo-HSCT to be accessible for treatment in developing countries could significantly improve patient survival outcomes.

Background: The purpose of this study is to synthesize evidence on disease-specific outcomes in patients with sickle cell disease (SCD) or transfusion-dependent beta-thalassemia (TDT) following allogeneic hematopoietic stem cell transplant (allo-HSCT).

Methods: A systematic literature review (SLR) was conducted in MEDLINE and Embase to identify publications up to May 2023, including patients with SCD or TDT treated with allo-HSCT. Occurrence of vaso-occlusive crises (VOCs) including acute pain, acute chest syndrome, priapism, and splenic sequestration in SCD, and red blood cell transfusion (RBCT) requirements in TDT were the main outcomes of interest. Transplant-related outcomes such as graft-versus-host disease (GVHD) and graft failure/rejection were summarized in the studies that reported main outcomes. Proportion of patients experiencing VOCs or RBCTs, GVHD, and graft failure/rejection after allo-HSCT were aggregated and descriptively reported with range across studies.

Results: Thirty-one SCD studies met inclusion criteria. Twenty-nine studies assessed for VOC and pain crisis events after allo-HSCT; 11 studies reported ≥1 VOCs after allo-HSCT in 6.9% of the 2,760 patients. Graft failure was reported in 14.4% (0.9%-18.8%, 14 studies) of patients, graft rejection in 5.5% (1.6%-100.0%, 12 studies) of patients, acute GVHD in 22.4% (1.6%-50.0%, 19 studies) of patients, and chronic GVHD in 20.4% (3.3%-57.1%, 14 studies) of patients. Seventy-eight TDT studies met inclusion criteria. Fifty-six studies reported that 8.8% of the 3,107 patients required RBCTs after allo-HSCT. Graft failure was reported in 5.4% (1.1%-80.0%, 21 studies) of patients, graft rejection in 7.5% (0.5%-42.9%, 50 studies) of patients, acute GVHD in 28.4% (5.2%-100.0%, 57 studies) and chronic GVHD in 15.2% (1.3%-50.0%, 51 studies) of TDT patients.

Conclusion: Based on this SLR, after allo-HSCT, a portion of patients with SCD continue to experience VOCs and a portion of patients with TDT continue to require RBCTs, in addition to experiencing GVHD and graft failure or rejection.

Background and purpose: Hemoglobinopathies are hereditary blood disorders affecting hemoglobin in red blood cells. This study aimed to determine the prevalence and types of hemoglobinopathies among newborns in Thumbay Teaching Hospital, Ajman-UAE, over three years (2020-2022), and to analyze demographic trends.

Method and population: A laboratory-based retrospective cross-sectional study was conducted, involving 6,050 newborns screened using High-Performance Liquid Chromatography (HPLC).

Results: We consider this study and its results as a new effort in the field of hemoglobinopathy research and management in Ajman in the United Arab Emirates. The final main findings revealed different hemoglobinopathy cases. In 2020 Two cases (2) involving Hb C variant were recorded, both of African origin (from Sudan and Egypt). The third case was Hb D variant which was also of African origin (Egypt). In 2021 no case was found. In 2022, the results showed a widespread of cases; A patient from Nigeria reported having Hb C, three cases of Hb D from Pakistan, two cases of Hb E trait from people in Bangladesh and India, one case of Hb S from Malawi, five cases of Hb S trait from people in Africa (two from Kenya, one from Tanzania), and two cases from Asian people from Yemen. The total number of detected hemoglobinopathies was 15 cases, accounting for a percentage of (0.2%).

Conclusion: The study reveals a diverse presence of hemoglobinopathies among newborns in Ajman and underscores the importance of newborn screening programs to facilitate early diagnosis and treatment, particularly in regions with high genetic disorder prevalence. The study revealed almost an obvious African origin of Hb C and S cases and Asian one of Hb E and D cases.

Background: Blood Group O donors with high antibody IgG anti-A and anti-B titers of 1:256 or higher was considered high antibody titer and generally referred to as dangerous donors because their plasma has the potential to haemolyse or agglutinate red blood cells in non-Group O recipients. Titration for the IgG anti-A and anti-B prior to transfusion is required to prevent transfusion reactions. There is a monthly blood collection of 5000 blood units per-month with ABO RhD distribution of A 27%, B 20%, O 48%, AB 5%, and Rh(D) negative 2%. This study aimed at determining the prevalence of high-titer immune anti-A and anti-B in blood group O donors at Mbale regional blood bank.

Methods: A total of 382 blood group "O" donors were randomly selected and recruited after obtaining informed consent during the period of May 2022-January 2023. The titration for the anti-A and anti-B hemagglutinins (IgG class) titers was done by use of the tube titration technique. Data were summarized as means, standard deviations, percentages, and frequencies then presented in the form of pie charts and tables.

Results: Of the recruited participants, 270(70.7%) were males. Total number of group O donors with high-titer were 27(7.1%) of which 15(55.5%) were male. The most frequent occurring antibody was Anti-B with 17/27 (62.9%). In male with high titer, anti-B was the most occurring and significantly raised, while anti-A was the most raised in female.

Conclusion: There is a high proportion of blood group O donors having high titers of anti-A and anti-B (dangerous group O donors), with the most raised antibody being anti-A, which compromises the quality and safety of the blood products. We recommend screening for high-titer anti-A and anti-B antibodies in all blood group O donated units to make them safe for transfusion to non-group O recipients, especially where large volumes of plasma are required.

Background: The use of blood transfusion in surgery is increasing, and the blood supply is getting tighter. The number of glioma surgeries is increasing year by year, and reports of studies on blood transfusion in glioma surgery are relatively rare.

Purpose: To investigate the risk factors for intraoperative blood (leukocyte-depleted suspended red blood cells and plasma) transfusion in glioma patients.

Patients and methods: We retrospectively analyzed the data of 200 glioma patients who had been operated on in a general teaching hospital in China from January 1, 2018 to March 31, 2022. In terms of whether blood transfusion (leukocyte-depleted suspended red blood cells and plasma) was used intraoperatively, patients were divided into a transfusion group (n=82) and a non-transfusion group (n=118). Multivariate Logistic regression analysis was conducted to identify the risk factors for intraoperative blood transfusion.

Results: The rate of intraoperative transfusion rate in the 200 glioma patients was 41%. Multivariate Logistic regression analysis showed that operation time, intraoperative blood loss ≥500 mL, vascular involvement, and the extent of tumor resection (total resection) were independent risk factors for intraoperative blood transfusion (P<0.05). Patient height was a protective factor against intraoperative blood transfusion (P<0.05).

Conclusion: The risk of intraoperative blood transfusion was higher in glioma patients with longer operation time, more intraoperative blood loss, vascular involvement, and total tumor resection. Clinically, efforts should be made to avoid these transfusion-related risk factors to minimize the risk of blood transfusion in patients.

In recent years, gene therapy and bio-engineered hemostatic molecules have revolutionized treatment for people with hemophilia. These innovative therapies aim to decrease treatment burden and improve patient quality of life. Additional novel therapies, including next-generation mimetics and agents that rebalance hemostasis, are currently being evaluated in clinical trials. Technological advances such as point-of-care musculoskeletal ultrasound and artificial intelligence may improve patient diagnostic and treatment outcomes. However, for the majority of patients with hemophilia worldwide, diagnosis and effective treatment are inaccessible. Achieving health equity for all hemophilia patients requires improved identification of barriers to optimal care, including socioeconomic status, race/ethnicity, gender, disease severity, inhibitor status, age, and use of Hemophilia Treatment Centers. Access to novel hemophilia therapies should be ensured for all patients. Approaches to improving equity include a decision-making partnership between the patient and clinician, stakeholder engagement, and pharmaceutical industry support. The development of novel hemophilia therapies should be leveraged with a patient-centered care approach to improve health equity for all patients.

Introductions: Spinach (Amaranthus hybridus) is a green vegetable containing 380 μg/100 g of vitamin K, while warfarin serves as an antagonist in inhibiting vitamin K epoxide reductase subunit C1 (VKORC). In this context, the co-administration of warfarin and spinach is frequently encountered among Indonesian patients, potentially leading to drug-food interactions. This study aimed to investigate the effect of concomitant administration of spinach on the pharmacokinetic and pharmacodynamic profile of warfarin in New Zealand White rabbits.

Methods: A total of 24 New Zealand White rabbits weighing about 1.5-2 kg were used in this study. For 16 days, these rabbits were given oral warfarin at a dose of 0.4 mg/kg BW by 10.00 am. Subsequently, 3 mL of blood samples were withdrawn in the lateral vein of the ear on the 13th and 16th days. The Prothrombin Time-International Normalized Ratio (PT-INR) is used to evaluate the pharmacodynamic profile, while the plasma concentration of S(R)-warfarin (Cp (AV)), half-life (t_½), area under the curve (AUC), volume of distribution (Vd), and clearance (C_L) are analyzed to determine the pharmacokinetic effects of warfarin.

Results: In the Fluconazole (FZ) group, there was a significant increase in the area under the curve (AUC) at maximum concentration (Cmax) after treatment, with a p-value of < 0.05. In the Amaranthus hybridus dose 1 (AH-1) and Amaranthus hybridus dose 2 (AH-2) groups, AUC and plasma drug concentration (Cp (AV)) were higher after treatment but the results of statistical analysis were not significant.

Conclusion: There was no pharmacokinetic or pharmacodynamic interaction between spinach (Amaranthus hybridus) and warfarin. Additionally, patients subjected to warfarin therapy could consume spinach with a recommended portion size below 100 grams per day.

Purpose: This study aimed to compare platelet count, platelet indices, lymphocyte, and systemic inflammation indices between surviving and non-surviving COVID-19 patients, measured at admission and on the eighth day of hospitalization.

Patients and methods: A retrospective cohort study was conducted on COVID-19 patients hospitalized at Hasan Sadikin General Hospital, Bandung, from March to December 2020. Patient characteristics and laboratory data were sourced from medical records and the Clinical Pathology Laboratory. Bivariate analysis was performed to determine the comparison of platelet indexes between Surviving and Non-Surviving COVID-19 patients depending on data distribution. Significantly correlated variables in Bivariate analysis were included in the ROC analysis, with the AUC used to identify optimal threshold values for laboratory parameters.

Results: Data from 132 patients were analyzed, with 106 (80.3%) surviving and 32 (19.7%) not surviving. Non-surviving patients had lower platelet count, PLTCT, and lymphocyte levels but higher MPV and PDW compared to survivors. Receiver operating characteristic (ROC) analysis revealed that on day 1, lymphocytes had a higher area under the curve (AUC) than MPV. On day 8, lymphocytes had the highest AUC, followed by platelet count, MPV, PLTCT, and PDW.

Conclusion: Platelet indices, lymphocyte counts, and systemic inflammation index have the potential to distinguish the severity of COVID-19.